Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) was used to study the anti-MRSA effect and preliminary molecular mechanism of the medicinal plant formula MZL-1 developed in the laboratory. The antibacterial effect of MZL-1 was confirmed by the double dilution method, and the relative conductivity, alkaline phosphatase activity change and scanning electron microscope observation were detected to analyze the effect of MZL-1 treatment on the destruction and integrity of the cell wall and membrane of MRSA. Flow cytometry was utilized to determine the effect of MZL-1 on MRSA for cell apoptosis. Network pharmacology was applied to explore the possible molecular mechanism of the anti-microbial effects of MZL-1. The result showed that the MIC of MZL-1 to MRSA was 7.5%. The increase in the activities of relative electric conductivity and alkaline phosphatase as well as the significant changes in morphology and damages observed by scanning electron microscopy indicated that MZL-1 obviously disrupted the integrity of MRSA cells and hence caused the overflow of the cell contents. Flow cytometry analysis found that a large number of cell apoptosis occurred in the early stage. Network pharmacology discovered 29 compounds and 23 target genes for MZL-1 in anti-microbial infection, and RELA may be the core gene. Gene Ontology(GO) enrichment analysis showed that target genes were mainly involved in the cell's response to small molecules, cytokines and transcription factors. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis found that the pathways involved mainly focused on inflammation, apoptosis, immune function, and bacterial and viral infections. Based on the current research, the formula MZL-1 might be potentially developed to be a plant-derived drug against MRSA and other drug-resistant pathogens and microbial infections.

Key words: medicine plant, MZL-1, anti-microbe, MRSA, mechanism